Hopkins researchers find a new test for prostate cancer screening

New studies of a blood protein recently identified at
Johns Hopkins, early prostate cancer antigen-2 (EPCA-2), may change the
way men are screened for prostate cancer — a disease that kills tens of
thousands of men every year.

Results showed that the EPCA-2 test was negative in 97
percent of the patients who did not have prostate cancer. Men with no
evidence of disease (regardless of their PSA levels), as well as the
control group of patients with other cancer types and benign conditions,
all had EPCA-2 levels below the cutoff.

In contrast, in a multi-institutional study published in
2003 in the Journal of Urology, PSA levels between 4 and 10 nanograms per
milliliter were shown to be accurate in identifying patients without
prostate cancer only 19 percent of the time.

In addition, 77 percent of the BPH patients had a level of
EPCA-2 lower than the cutoff point. Getzenberg says this is well within
the likely percentage range of BPH patients who are prostate-cancer free.
He says this result was encouraging since BPH is often associated with
elevated PSA levels, leading to misdiagnosis and unnecessary biopsies.

When it came to correctly identifying patients with
prostate cancer, EPCA-2 levels at or above the cutoff were detected in 90
percent of the men with organ-confined prostate cancer and 98 percent of
the men with disease outside of the prostate. Overall, in this study, the
EPCA-2 test detected 94 percent of the men with prostate cancer.

I have currently been using a test called pca3 Plus, which is a urine test done after a rectal exam to help determine if I should perform a biopsy. If this test is as good as it sounds, it will likely replace PSA. I look forward to seeing how the studies come out.

23 Responses to Hopkins researchers find a new test for prostate cancer screening

Dr. Savatta:
My husband recently had a PCA3 test done at Bostwick Laboratories. Their cutoff for â€œpositiveâ€ results is 10 â€“ i.e. any value over 10 is considered â€œpositiveâ€. In doing a fair amount of reading on this subject (for obvious reasons), I discovered that a Dr. Fradet in the Netherlands considers an optimal cutoff to be 35. My husbandâ€™s result was 27.2. Bostwick labeled this â€œpositiveâ€. My understanding is that the other lab in the US that does this test (Ameripath) uses the value of 35 as a cutoff. If Ameripath had done the test, his result would have been â€œnegativeâ€.
We consider this test to have been a waste of time and money. The insurance company amazingly covered most of Bostwickâ€™s charge. Our responsibility is under $25.
What is your opinion on the difference in cutoff values for this test? Is it â€œready for prime timeâ€ yet?
BTW, as a result of the â€œpositiveâ€ result from Bostwick, my husband had a biopsy last Thursday, 8/24. We are awaiting the results.
Thank you for your time.

Thank you for your question and Ive asked myself the same thing.
It will be a blog entry by itself in the near future.
A decent review that you may have read can be found at:http://www.urologytimes.com/urologytimes/article/articleDetail.jsp?id=357764&searchString=fradet
The way the test works is it measures the amount of a substance in urine (RNA). I have not been using it long enough to tell you if it is ready for primetime, but I can tell you how and why I use it.
If someone has a normal PSA and prostate exam and are very concerned about prostate cancer, I will perform a PCA3 test. These patients usually have a strong family history. I have been sending my specimens to Bostwick as well. I do this since even people with low PSAs and normal exams can have cancer. I have performed surgery on several patients that were diagnosed like this.
Also, If I have done a biopsy which is negative and I am still concerned about the PSA, I will do the PCA test and only perform a biopsy if it is positive.
I agree with you that the number seems arbitrary and the new “normal” value of PCA at Bostwick is 11, which was increased from 10 recently. I am told that studies show that 57% of patients with a positive result have cancer.
I explain why I am doing the test and how it will help my management. I usually use it more to avoid another biopsy if it is negative than to do a biopsy if it is positive.
I will wait until I have more experience with it prior to recommending it across the board. For now, I think it is a useful test for some patients.
The trade off should be that you should diagnose more prostate cancer by using the test, but will likely do more biopsies that are negative as well.
I am uncertain if the difference in normal values has to do with the way each lab runs the test, but this may be the case. If this is the case it should be standardized across all labs.
The other important factor to consider is that the normal value gets increased, then the amount of cancer that are found decreases (sensitivity), but the amount of biopsies that are negative also decreases.
I am sure other urologists would disagree with me as there are other opinions on this, but when it comes to these kind of areas, I always ask myself: What would I want done if it was my dad that was in that situation.
Dr Savatta

Dr. Savatta:
Thank you for the quick and clear reply.
To clarify my husbandâ€™s case, and in all fairness to everyone, the urologist wanted to do a biopsy but my husband had concerns about infection. He is 2 Â½+ years post-op right hip replacement and has done very well with that. When we read about the non-invasive PCA3 test, we suggested it to the urologist who agreed to do it instead of an immediate biopsy. My husbandâ€™s PSA had jumped from 1.8 in November 2005 to 2.6 in June 2006 (age 64). Four DREâ€™s since June have been done and nothing was felt by anyone (primary doc and two urologists). Had the PCA3 come back â€œnegativeâ€, the urologist would have seen him again in three months. When it came back â€œpositiveâ€, there was no choice but to do a biopsy. Results will be obtained at a 9/6 follow-up appointment.
Thanks again.

Thanks for your input.
I had an old blog post I re-classified into the screening category.http://www.njurology.com/RoboticSurgeryBlog/2006/06/new_normal_psa_velocity.php
This brings us to a use of the PCA that I do not like as much. What if someone needs a biopsy and never has had one before.
That’s a tough question. I usually use age adjusted PSAs and age adjusted PSA velocities. If someone would need a biopsy, I do not like performing a PCA instead and not biopsying if negative. If there are extenuating circumstances, like someone who needs to be on blood thinners or has an increased rick of infection, then I may offer the PCA as a substitute, but would still recommend biopsy first.
I had a patient who I saw in second opinion once who had a mildly elevated PSA, but a normal UPMT3 test (this was the previous generation PCA3 test)and was not biopsied who later was found to have cancer by another urologist.

Dr. Savatta:
As a follow-up to my post of last week, I wanted to let you know that my husband’s biopsy was negative. Apparently he is among the 42% of patients who receive “false positive” results on the PCA3Plus test.
The urologist wants to see him again in four months and has ordered both PSA and free PSA tests.
Thank you, again, for maintaining this valuable source of information for patients.

Thanks for the update and Im glad you had good news.
I did speak to my rep from Bostwick who informs me that the reagents and test are the same in both labs. Bostwick sets their numbers to catch more cancers at the expense of having more false positives.
To quote them:
Bostwick laboratories uses a cutoff of > 11 for a positive result. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) are 96%, 45%, 58% and 93% for PCA3Plus offered by Bostwick Laboratories. Ameripath uses a cutoff of 35. The sensitivity is 58%, and specificity is 74% for PCA3 ProfileR offered by Ameripath.
Its the same idea as PSA. Should you have a biopsy with a PSA of 2.6? The chance of having prostate cancer is 22% with a PSA from 2.6 to 4.0, so I say yes. Other urologists would disagree with me.
Dr Savatta

Dr. Savatta,
I really like how you try and put yourselves in the patient’s shoes.
Question…if a 57 year old male had a history of prostitis and felt they were having similiar symptoms with a normal rectal exam…a 3.5 PSA…BUT a PCA 3 Plus of 26.3 have a biospy?? I believe the answer is yes, however, could prosititis escalate the number in the PCA 3 Plus?? I know it can escalate the PSA number.
Thanks…god bless you.
D.Hale

Prostatitis and PCA plus:
My understanding is that the PCA plus test should not be altered by infection.
PSA can definitely be altered by infection including chronic prostatitis. I usually will biopsy a healthy man with a PSA over 2.5 (especially if he is under 60 years old) if there is not evidence of an active infection. If there are inflammatory cells in the urine or new symptoms I will try 2 weeks of antibiotics first and then repeat the PSA.
If I happen to perform a PCA 3 test, than I will perform a biopsy if the number comes back above 11.
What I do before performing any test is explain to the patient the pros and cons and then what number will make me recommend a biopsy. I find it is easier to set a definite number at the time the test is done than deciding if I should perform a biopsy or not after the test comes back.
If a patient changes his minds in having a biopsy, we can always repeat the test in 3 months (or 6).
I understand the risk of infection and bleeding, but prefer to diagnose prostate cancer in its earlier stages thinking that I should save more lives.
Dr Savatta

Dr. Savatta,
Thanks for your speedy reply. Would I be correct in assuming that the above stats would generally indicate a probability of about 30% likelihood of cancer?? And, with these numbers as aforementioned would the cancer usually be in the early stages?
And, one final question…if you have these numbers with evidently the gene are you likely to get Prostate Cancer in your lifetime…therefore requiring PCA 3 fOLLOW up with what frequency?
Thanks for your candor..god bless.
D. Hale

For a PSA of 3.5, the risk of having cancer is about 23%.
A PCA of 26 should have a 55% risk of having cancer.
A guess of 30-40% I think would be reasonable.
If cancer is found, it will most likely be very early stages.
I’m not sure on how to follow PCA 3 tests yet. The higher the number, the higher the risk of cancer. I think a test every 6 months is reasonable, or at least a PSA every 6 months.
There is a web site that helps estimate risk of prostate cancer and high grade disease that you may find helpful:http://www.compass.fhcrc.org/edrnnci/bin/calculator/main.asp

Dr. Savatta,
Thank you for all of your info…hopefully, it helps give a better understanding to others with the same questions.
One final question…if the total PSA is 3.5, and the PSA 2 is 21…can both be impacted by prosititis?? I know that the total PSA can be…but how about the PSA 2?? If antibiotics takes the scores down is that more likely an infection?? Believe me I am still having a biopsy…thanks.
D Hale

My recent (June 28,2007) PCA3plus test report from Bostiwick Lab shows 15. They say the cut-off is 35, and thus I am negative.
Did they change the cut-off from 10 to 11 and to 35?
I am 71 now and had elevated PSA since 1999. 5.9 Total PSA with 0.4 Free PSA. Biopsy reported High Grade PIN.
In 2000, PSA kept going up to 7.1 and two more Biopsies were normal.
From 2001 to 2005, PSA went down to 4.4 but backing up to 8.1 in 2006.
I had another Biopsy this year and the result is still negative. But, my PSA is now 12.4.
The DRE (performed by my regular Physician and an Urologist alternately) were always normal. My prostate is enlarged but PSA per volume is still too high.
Aside form DRE and PSA test every 3-month, what else could I do?

Bostwick changed their value for positive to 35 about 1 year ago.
Ameripath has always been 35.
Your other questions are too complex for this blog and should be addressed with your urologist. By itself a high PSA is not harmful and not everyone with a high PSA has prostate cancer.
Good luck,
Dr Savatta

Dear Dr Savatta,
Following an initial PSA test giving a reading of 5.4, I have had a Bostwick PCA3+ test and the results have come back as 6.5, a low value according to all the information I have read.
However, I am having difficulty in fully understanding the Sensitivity and Specificity values as given by Bostwick. They give a sensitivity value of 57% for PCA3+ compared to a value of 83% for a PSA greater than 4 test. On specificity they quote 75% for the PCA3+ test and 17% for the PSA test.
Am I right to interpret this as follows.
The sensitivity value is the % of people tested who have prostate cancer who are identified as such by the test. The specificity figure is the % of people who do not have prostate cancer who are identified as negative.
Thus the PCA3+ test is very good at saying you do not have prostate cancer if you do not have it, but not so at saying you do have it if you actually do, and the PSA test is the other way round.
Now my problem, given that 11 out of 12 men are likely not to have prostate cancer how do I interpret the sensitivity and specificity figures to give me the chances of my having or not having prostate cancer.

In the preceding question, the specificity of PSA does not seem correct. I am curious about your source. A good description of specificity can be found at wikipedia. I think the first statement is correct, but then you are mixing in predictive values, which are related, but different.
Patients should talk to their own urologist, but my philosophy is to use the PCA3 test after a biopsy is negative.
I have seen patients that have cancer with a negative PCA3 test. If the PSA rises after a negative biopsy, I look at the PCA3 test more often.
Also, once the PSA is between 4-10, there is about a 30% chance of having prostate cancer. I would imagine that if the PCA3 is low, then this is lower, but I am not sure exactly how low.

Dear Dr. Savatta,
Obviously, we have a long way to go in developing an accurate test protocol for prostate cancer. My case is a good example. Three years ago (at age 66) my PSA doubled up to 4.9 and a resulting biopsy confirmed the presence of prostate cancer. I have opted to employ an aggressive watchful waiting regime. The results are a current PSA of 1.2 and a PCA3 of 10. Clearly, were I to walk into another urologist’s office, provide no history, and take the two tests, no cancer would be suspected and no biopsy performed. I do not envy you in attempting to give informed, accurate guidance to your patients.

Dear Dr. Savatta,
Thank you for all the time and effort you put into facilitating our understanding.
I am 48 years old. I have symptoms associated with prostatitis (pain during ejaculation). My PSA’s have been fairly high but steady, around 10 or 11. I have had 2 negative biopsies. In the second biopsy the pathologist indicated highly inflamed tissue, which makes me think that I may have obtained prostatitis from the first biopsy. Antibiotics (several types) have not been successful in decreasing my symptoms or lowering my PSA’s. Semen and urine cultures have also been negative in terms of determining the presence of bacteria. DRE’s have been normal. At this point my urologist is recommending a 3rd (saturation) biopsy. I have been doing research and found that the pca3 plus test might be a useful tool, but I also found that the epca-2 might be even better for this kind of situation. Do you have an opinion in terms of whether I should go ahead with the pca3 plus or wait until epca-2 becomes available?
Thank you for your time.
Sincerely,
Patrick Scott

I can not give medical advice without a full evaluation, and there are many opinions that I would consider valid.
I usually offer what is available, which is a free PSA and a PCA3 test. Neither are 100% accurate, but help some.
I have also used a long course of antibiotics of 3-4 weeks, although this has risk as well.
As long as there was an adequate biopsy that includes the transitional zone on the second biopsy, I would feel comfortable following the PSA closely.
The main concern is younger patients, where it is more appropriate to be aggressive and look into saturation biopsies as well.
Good luck,
Dr Savatta

I am a 58 yr old male. PSA in Dec ’08 of 5.03 followed by 4.74 in Jan 09 followed by a negative biopsy in Jan 09.
My urologist recommended a follow up PSA in six months which came back 10.0 yesterday. PCA3 Plus results are pending. I start 10 days of Cipro today.
I noticed in other blog entries that you set a level above which another biopsy is indicated. Is that level across the board for all patients or customized for each individual?
Also, what is your experience with negative biopsy results that subsequently cancer is found?
Thank you for your advice in advance.

There are no set limits for repeat biopsies. A trial of antibiotic to see if the rise is due to inflammation is reasonable, as well as a PCA3 test.
In general, repeat biopsies are less likely to yield cancer than the original and the odds go down with each negative biopsy. I have found cancer even after 4-5 negative ones.
Usually the cancer found in repeat biopsies is lower in volume than original biopsies.
This management has to be individualized.

Thanks, Dr. Savatta for your speedy reply. I am hoping for a negative on the PCA3.
Do you normally go directly to biopsy should the PCA3 results come back higher than 35? Also, if the PCA3 comes back lower, do you recommend repeating the PSA?
Thanks for your information.

My husband in 2006 had two biopsy’s, result HGPIN watch and wait. He chose not to get PSA done again until 7-2009, July PSA 6.3, repeat in August, first antibiotics 10 days then another PSA 9.6. Then end of August PCA3 result positive high score of 173. We then switched uriologist, for several reasons. Just saw the new one last week, he wants to wait till mid November to do the biopsy, as that is when new surgery center opens. I feel like since the score PSA went up and PCA3 is extremely high and he has history of HGPIN we should not wait 5 weeks. Would you agree not to wait so long? Should a MRI be done before the Biopsy? Anything else before biopsy, don’t want to miss anything or have to repeat again. Husband just turned 63.

I agree that a prostate biopsy should be performed. I normally would schedule a prostate biopsy within 2-4 weeks, but 5 weeks should not cause a major difference in pathology reports. Normally prostate cancer is slow growing.
I usually perform MRIs for recurrent biopsies. A biopsy has not been done in 3 years in this case, so a biopsy without an MRI is also OK. If done an MRI has to be done with specific software or an endorectal coil. I usually order them with 3TP software that removes the need for an endorectal coil.

All content available on this site is intended for informational and educational purposes only. This site does not provide medical advice. The information should not be construed as a replacement or substitute for professional medical treatment or for professional medical advice. There is no replacement for personal medical treatment and advice from your personal physician.